1 Summary: 2 Near infrared spectroscopy (NIRS) based continuous measures of cerebrovascular reactivity 3 pose a convenient, and potentially non-invasive, method of monitoring cerebral autoregulation in 4 adult traumatic brain injury (TBI).1,2 These indices are based on the assessment of the 5 correlation between slow-wave fluctuations in a measure of pulsatile cerebral blood volume 6 (CBV), such as NIRS total oxygen index, and a measure of cerebral blood flow driving pressure, 7 such as mean arterial pressure (MAP) or cerebral perfusion pressure (CPP).3,4 To date, 8 literature has experimentally validated these indices in animal models of cerebral 9 autoregulation, with clinical data supporting moderate associations with ?gold standard? invasive 10 measures of cerebrovascular reactivity via rough estimates.2,5?7 However, further investigation 11 into NIRS based cerebrovascular indices is required. The following aspects regarding NIRS 12 cerebrovascular reactivity indices require answering, prior to widespread clinical application. 13 First, assessment of the time-series relationships between gold standard ICP indices, such as 14 pressure reactivity index (PRx), and indices derived from NIRS is required. Demonstrating 15 strong co-variance over time between PRx and NIRS indices would provide confidence in their 16 application clinically for monitoring in adult TBI. Second, time-series modelling of intra-cranial 17 pressure (ICP)-derived indices using non-invasively derived NIRS indices could become a 18 means to provide surrogate assessment of PRx. Though conducted with transcranial Doppler, 19 this has never been attempted with NIRS.8 Third, the association between cerebral 20 autoregulation during the acute intensive care unit (ICU) phase and that during long-term follow 21 up has never been assessed using continuous physiologic indices. There is the potential that 22 those patients with impaired cerebrovascular reactivity during the acute phase of illness, will 23 have ongoing dysfunction at 3, 6 and 12 months post-injury. Finally, the association between 24 NIRS based non-invasive indices of cerebral autoregulation, both during the acute and long- 25 term follow-up, with measures of global functional outcome and patient quality of life have never 26 been assessed. There exists the potential for a direct association between NIRS indices in the 27 acute phase and long-term morbidity/mortality. Furthermore, persistent symptomatology during 28 in the long-term may be related to ongoing autoregulatory dysfunction, as measured non- 29 invasively through NIRS. This prospective pilot study will assess the above questions, 30 measuring NIRS based continuous measures of cerebrovascular reactivity during acute and 31 long-term phases in adult TBI.